A clinically relevant sheep model of orthotopic heart transplantation 24 h after donor brainstem death

Background Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard therapy for severe/end-stage cardiac disease, but is limited by a global donor heart shortage. Consequently, innovative solutions to increase donor heart availability and utilisation are rapidly expanding. Clinically relevant preclinical models are essential for evaluating interventions for human translation, yet few exist that accurately mimic all key HTx components, incorporating injuries beginning in the donor, through to the recipient. To enable future assessment of novel perfusion technologies in our research program, we thus aimed to develop a clinically relevant sheep model of HTx following 24 h of donor BSD. Methods BSD donors (vs. sham neurological injury, 4/group) were hemodynamically supported and monitored for 24 h, followed by heart preservation with cold static storage. Bicaval orthotopic HTx was performed in matched recipients, who were weaned from cardiopulmonary bypass (CPB), and monitored for 6 h. Donor and recipient blood were assayed for inflammatory and cardiac injury markers, and cardiac function was assessed using echocardiography. Repeated measurements between the two different groups during the study observation period were assessed by mixed ANOVA for repeated measures. Results Brainstem death caused an immediate catecholaminergic hemodynamic response (mean arterial pressure, p = 0.09), systemic inflammation (IL-6 - p = 0.025, IL-8 - p = 0.002) and cardiac injury (cardiac troponin I, p = 0.048), requiring vasopressor support (vasopressor dependency index, VDI, p = 0.023), with normalisation of biomarkers and physiology over 24 h. All hearts were weaned from CPB and monitored for 6 h post-HTx, except one (sham) recipient that died 2 h post-HTx. Hemodynamic (VDI - p = 0.592, heart rate - p = 0.747) and metabolic (blood lactate, p = 0.546) parameters post-HTx were comparable between groups, despite the observed physiological perturbations that occurred during donor BSD. All p values denote interaction among groups and time in the ANOVA for repeated measures. Conclusions We have successfully developed an ovine HTx model following 24 h of donor BSD. After 6 h of critical care management post-HTx, there were no differences between groups, despite evident hemodynamic perturbations, systemic inflammation, and cardiac injury observed during donor BSD. This preclinical model provides a platform for critical assessment of injury development pre- and post-HTx, and novel therapeutic evaluation.

P.050 Perspectives on the use of ancillary tests for determining neurological death: a survey of Canadian intensivists

Background: Ancillary tests are indicated to diagnose death by neurological criteria whenever clinical neurological examination is unreliable, but their use is variable and subject to debate. Methods: Survey of Canadian intensivists providing care for potential organ donors. We included closed-ended questions and different clinical scenarios regarding the use of ancillary tests. Results: Among 550 identified intensivists, 249 completed the survey. Respondents indicated they would be comfortable diagnosing death based on neurological examination without ancillary tests in the following scenarios: movement in response to stimulation (48%), spontaneous peripheral movement (31%), inability to evaluate upper/lower extremity responses (34%) or both oculocephalic and oculo-caloric reflexes (17%), presence of high cervical spinal cord injury (16%) and within 24 hours of hypoxemic-ischemic brain injury (15%). Furthermore, 93% agreed that ancillary tests should always be conducted when a complete neurological examination is impossible, 89% if there remains possibility of residual sedative effect and 59% in suspected isolated brainstem death. Conclusions: Our findings suggest that Canadian intensivists have different perceptions on what constitutes a complete and reliable clinical neurological examination for determining death by neurologic criteria. Some self-reported practices also diverge from national recommendations. Further investigation and education are required to align and standardize medical practice across physicians and systems.

Biopsychosocial Aspect of Pregnant Women Suspected Brainstem Death

Objectives: Diagnosis of brainstem death and the vital organ function support in the pregnant woman to prolong gestation to attain fetal viability is still controversial. The decision is influenced by ethical and legal issue in the country. Another consideration is the hospital cost and health insurance coverage. This article purpose is to report a case and discuss the biopsychosocial aspect of this issue, so the doctors know how to decide a similar case.Methods: We reported a suspected brainstem death in pregnant women and discussed the holistic approach.Case: This case is a-38-year-old women, third pregnancy, 22 weeks of gestation, referred from the secondary hospital in a comatose condition. She was diagnosed with brainstem dysfunction due to intracranial mass and cerebral oedema. She wasn't diagnosed with brainstem death due to the electrolyte imbalance that can cause this condition. We did the multidisciplinary management approach. We decided the termination of pregnancy would only be performed if the fetus reaches 28 weeks of gestational age (with survival rate on perinatology is 31%). From the husband point of view, since the attending doctors have not declared the mother to be dead, then the husband still want to keep the mother in full life support. The patient and the fetus died on the 8th day of hospitalization. The patient was fully paid for by Indonesian Health Insurance.Conclusion: Maternal brainstem dysfunction and brainstem death during pregnancy are rare. In Indonesia, ethical and legal consideration to keep both mother and fetus are appropriate with the general social, cultural, and religious values. However, we recommend managing every single case individually with an intensive multidisciplinary approach due to the possibility of the different personal value of the patient.Keywords: brainstem dysfunction, brain death, pregnancy, fetal, ethic, legal. Abstrak Tujuan: Diagnosis kematian batang otak dan dukungan fungsi organ vital pada perempuan hamil untuk melanjutkan kehamilannya sampai janin dapat hidup jika dilahirkan masih kontrovesi. Keputusan ini dipengaruhi oleh etik dan hukum di suatu negara. Pertimbangan lainnya adalah biaya perawatan rumah sakit dan cakupan asuransi kesehatan. Artikel ini bertujuan melaporkan sebuah kasus dan mendiskusikan aspek biopsikososialnya, sehingga para dokter dapat mengambil keputusan pada kasus lain yang serupa.Metode: Kami melaporkan kasus perempuan hamil dengan kecurgaan kematian batang otak dan mendiskusikan pendekatan holistiknya.Hasil: Kasus perempuan usia 38 tahun, kehamilan ketiga, 22 minggu, dirujuk dari rumah sakit sekunder dalam kondisi koma. Pasien didiagnosis dengan disfungsi batang otak akibat massa intracranial dan edema serebri. Pasien tidak didiagnosis dengan meti batang otak karena kondisi ini masih dapat dikarenakan gangguan keseimbangan elektrolit. Kami melakukan pendekatan multidisiplin. Diputuskan terminasi kehamilan akan dilakukan hanya jika janin mencapai usia kehamilan 28 minggu (dengan harapan hidup dari perinatology 31%). Dikarenakan dokter belum mengatakan pasien sudah meninggal, suami pasien menginginkan pasien dalam topangan alat. Pasien dan janinnya meninggal pada hari ke-8 perawatan. Pembiayaan pasien dengan menggunakan BPJS.Kesimpulan: Disfungsi batang otak dan kematian batang otak selama kehamilan adalah kasus yang jarang. Di Indonesia, etik dan hukum yang berlaku untuk menjaga kehidupan ibu dan janin sesuai dengan nilai sosial, budaya, dan agama. Namun demikian, kami merekomendasikan mlakukan tata laksana setiap kasus secara individu dengan pendekatan multidisiplin dikarenakan perbedaan nilai pribadi pasien dan keluarga.Kata kunci: disfungsi batang otak, etik, hukum, janin, mati batang otak, kehamilan.

New perspectives on brain death

Brain death, or death by neurological criteria (BD/DNC), has been accepted conceptually, medically and legally for decades. Nevertheless, some areas remain controversial or understudied, pointing to a need for focused research to advance the field. Multiple recent contributions have increased our understanding of BD/DNC, solidified our practice and provided guidance where previously lacking. There have also been important developments on a global scale, including in low-to-middle income countries such as in South America. Although variability in protocols and practice still exists, new efforts are underway to reduce inconsistencies and better train practitioners in accurate and sound BD/DNC determination. Various legal challenges have required formal responses from national societies, and the American Academy of Neurology has filled this void with much needed guidance. Questions remain regarding concepts such as ‘whole brain’ versus ‘brainstem’ death, and the intersection of BD/DNC and rubrics of medical futility. These concepts are the subject of this review.

Ethical, legal, and end-of-life decision-making

All of those working in paediatric intensive care will be faced with difficult decisions and will be looking after children at the end of their lives. Chapter 12 addresses the principles of medical ethics. It explains the assessment of ‘Gillick’ competence and obtaining consent from children, when to consider treatment limitation and involve the palliative care team, and, in some cases, where legal advice should be sought. Brainstem death is defined, and guidance is provided on how to perform brainstem death tests, including the use of ancillary tests and specific requirements for children under the age of 2 months. The chapter discusses end-of-life care in the Paediatric Intensive Care Unit, including organ donation in children. The final scenario explores the role of the intensivist in resource allocation decision-making and intensive care triage.

Brainstem death and prolonged disorders of consciousness

Advances in resuscitation and the advent of modern intensive care techniques to support the circulation challenge the simple definition of death in terms of loss of spontaneous circulation (‘cardiac death’). Instead, death is now better regarded as an irreversible loss of the capacity for consciousness combined with irreversible loss of the capacity to breathe. Since the brainstem is required for both consciousness and spontaneous breathing, irreversible loss of brainstem function (e.g. after trauma, haemorrhage, or hypoxia/ischaemia) defines the state of ‘brainstem death’. Clinical criteria for the diagnosis of brainstem death have been published, but practice varies around the world. Brainstem death lies at the extreme end of this spectrum and is, by definition, permanent. Unlike those with brainstem death, patients with prolonged disorders of consciousness may survive for many years without physiological support. The care of such patients has huge social, societal, ethical, and economic implications.

Death and dying

This chapter discusses death and dying, and includes discussion on confirming death using neurological criteria (brainstem death), withdrawing and withholding treatment, organ donation after brain death (DBD), and organ donation after circulatory determination of death (DCD). Death is common in the intensive care unit (ICU) and it is important to identify patients whose condition meets the criteria for brainstem death testing as well as patients where continued treatment is not considered to be in their overall best interests. Confirming death using neurological criteria allows the relatives to be presented with the certainty of a diagnosis of death whether organ donation is possible or not. Decisions to withraw treatment are common in the ICU and are associated with approximately 50% of all deaths in the ICU. The decision is made by the multidisciplinary team in consultation with the patient’s relatives and taking into account the patient’s values and preferences. In both situations the possibility of organ donation should be considered and explored, and, when it is a possibility, it should be routinely offered to the relatives as an end-of-life care option.